Role of <em>MLH1</em> methylation in esophageal cancer carcinogenesis and its clinical significance

Abstract

Abstract:The mutL homolog-1 (MLH1) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20-2.66), advanced tumor grade (OR=3.7; 95% CI =2.37-5.77), lymph node metastasis (OR=2.65; 95% CI =1.81-3.88), distant metastasis (OR=7.60; 95% CI =1.23-47.19), advanced clinical stage (OR=4.46; 95% CI =2.88-6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00-2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC.

A systematic review and meta-analysis approach on diagnostic value of MLH1 promoter methylation for head and neck squamous cell carcinoma

“…Epigenetic silencing of MLH1 promoter methylation can cause mismatch repair (MMR) deficiency, which may cause insertion or deletion mutations in repeated sequences. [9] The MLH1 promoter methylation has been reported as a well-established biomarker in several types of cancer, such as esophageal cancer, [10] colorectal cancer, [11] non-small cell lung cancer, [12] gastric cancer, [13] papillary thyroid cancer, [14] and bladder cancer. [15]…”

Effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells

“…The inactivation of p53 or p16 is considered to be one of the main features of malignant tumors (25). MLH1 is responsible for DNA mismatch repair, and the methylated hMLH1 has been frequently identified in many cancers, for instance, colorectal and esophageal cancer (26,27). In this study, an MSP assay was used to detect the methylation levels in the promoter region of p53, p16 and hMLH1.…”